Journal article

Publication year: 1998

Pages: 25320-25328

Journal: Journal of Biological Chemistry

Volume number: 273

Issue number: 39

DOI Link: https://doi.org/10.1074/jbc.273.39.25320

Publisher: Elsevier

Abstract: 

Secretory, membrane, and lysosomal proteins undergo covalent modifications and acquire their secondary and tertiary structure in the lumen of the endoplasmic reticulum (ER). In order to pass the ER quality control system and become transported to their final destinations, many of them are also assembled into oligomers. We have recently determined the three-dimensional structure of lysosomal aspartylglucosaminidase (AGA), which belongs to a newly discovered family of homologous amidohydrolases, the N-terminal nucleophile hydrolases. Members of this protein family are activated from an inactive precursor molecule by an autocatalytic proteolytic processing event whose exact mechanism has not been thoroughly determined. Here we have characterized in more detail the initial events in the ER required for the formation of active AGA enzyme using transient expression of polypeptides carrying targeted amino acid substitutions. We show that His¹²⁴ at an interface between two heterodimers of AGA is crucial for the thermodynamically stable oligomeric structure of AGA. Furthermore, the side chain of Thr²⁰⁶ is essential both for the proteolytic activation and enzymatic activity of AGA. Finally, the proper geometry of the residues His²⁰⁴–Asp²⁰⁵ seems to be crucial for the activation of AGA precursor polypeptides. We propose here a reaction mechanism for the activation of AGA which could be valid for homologous enzymes as well.

Harvard Citation style: Saarela, J., Laine, M., Oinonen, C., Jalanko, A., Rouvinen, J., Peltonen, L., et al. (1998) Activation and oligomerization of aspartylglucosaminidase, Journal of Biological Chemistry, 273(39), pp. 25320-25328. https://doi.org/10.1074/jbc.273.39.25320

APA Citation style: Saarela, J., Laine, M., Oinonen, C., Jalanko, A., Rouvinen, J., Peltonen, L., & Ritva, T. (1998). Activation and oligomerization of aspartylglucosaminidase. Journal of Biological Chemistry. 273(39), 25320-25328. https://doi.org/10.1074/jbc.273.39.25320